INHIBITION OF PROLYL HYDROXYLASE ACTIVITY AND COLLAGEN BIOSYNTHESIS BY FIBROSTATIN C, A NOVEL INHIBITOR PRODUCED BY STREPTOMYCES CATENULAE SUBSP. GRISEOSPORA NO. 23924

Abstract

Fibrostatin C, a novel prolyl hydroxylase inhibitor produced by Streptomyces catenulae subsp. griseospora No. 23924, inhibited the activity of purified chick embryo prolyl hydroxylase by about 50% at a concentration of 2.9×10^-5 M. The inhibition was mixed type with respect to (Pro-Pro-Gly)₅ with a Ki of 2.1×10^-5 M. When an excess of ferrous ions or ascorbate was added to the reaction mixture, the inhibition was negligibly or slightly reversed, respectively.
Fibrostatin C, when administered intraperitoneally at 1 mg/kg/day or orally at about 100mg/kg/day as a dietary admixture, significantly inhibited estradiol-17β stimulated collagen biosynthesis in the uterus of the immature rat.